title: Protein kinase C delta mediated cytotoxicity of 6-Hydroxydopamine via sustained extracellular signal-regulated kinase 1/2 activation in PC12 cells.
abstract: OBJECTIVE
  The incidence of Parkinson's disease (PD) is increasing as the global population ages. 6-hydroxydopamine (6-OHDA) can induce PD-like neuropathology and biochemical changes in both in vitro and in vivo models. Therefore, clarification of the molecular mechanism of 6-OHDA-induced cell death might contribute to the understanding of the pathogenesis of PD.
  
  
  METHODS
  With this goal in mind, we investigated the role of protein kinase C delta (PKC delta) in 6-OHDA-dependent death using the pheochromocytoma cell line, PC12. Cells were treated with 6-OHDA to induce toxicity with or without pretreatment using rottlerin (a PKC delta inhibitor), bisindolylmaleimide I (a general PKC inhibitor), Gö6976 (a PKC inhibitor selective for calcium-dependent PKC isoforms), or phorbol-12-myristate-13-acetate (PMA, a PKC activator).
  
  
  RESULTS
  Phorbol-12-myristate-13-acetate decreased cell survival and increased the rate of apoptosis while rottlerin increased cell survival and decreased the rate of apoptosis. In contrast, neither bisindolylmaleimide I nor Gö6976 affected 6-OHDA-induced cell death. Western analysis demonstrated that phosphorylation of PKC delta on Thr 505 as well as extracellular signal-regulated kinase (ERK) phosphorylation increased after exposure to 6-OHDA. This increase in PKC delta phosphorylation was potentiated by PMA. However, rottlerin attenuated the 6-OHDA-stimulated increase in PKC delta and ERK phosphorylation.
  
  
  CONCLUSIONS
  These data suggest that PKC delta, rather than classic-type PKC (alpha, beta1, beta2, gamma), participates in 6-OHDA-induced neurotoxicity in PC12 cells, and PKC delta activity is required for subsequent ERK activation during cell death.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fan
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Yan-Qiao
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Jiang
authors.forename: Yi-Na
authors.initials: YN
authors.lastname: Zhang
authors.forename: Chao-Qi
authors.initials: CQ
authors.lastname: Yan
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity*; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats
chemical_list: D018663:Adrenergic Agents; D016627:Oxidopamine; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: 6-Hydroxydopamine,; Apoptosis,; Extracellular signal-regulated kinases (ERK),; Parkinson’s disease,; Protein kinase C,; Rottlerin; Subtype delta,